Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism
Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism
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DOI：
10.1093/ndt/gfaa302
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发表时间：
2022-07-26
影响因子：
6.1
通讯作者：
de Seigneux, Sophie
中科院分区：
文献类型：
--
作者：
Legouis, David;Faivre, Anna;de Seigneux, Sophie
葡萄糖水平在任何时候都受到严格控制。葡萄糖异生是从非己糖前体合成葡萄糖的代谢途径。葡萄糖异生对于葡萄糖稳态是至关重要的，特别是在禁食或应激条件下。肾脏对系统性血管新生的作用越来越被人们所认识。在吸收后阶段，肾脏约占内源性造血的40%，主要发生在肾脏近端小管。肾脏再生的主要底物是乳酸盐，该过程受胰岛素和细胞葡萄糖水平调节，但也受酸中毒和应激激素调节。因此，肾脏在应激条件下维持葡萄糖和乳酸稳态中起重要作用。急性和慢性肾脏疾病以及近端肾小管损伤对肾脏再生的影响还没有得到很好的研究。近年来的研究表明，在实验性和临床急性肾损伤中，肾再生障碍可显著参与全身代谢紊乱，从而改变预后。本文综述了肾脏再生的生物化学、肾脏再生的现有知识、肾脏疾病中肾脏再生的改变以及这一基本生物学过程在人类生物学中的临床意义。
Glucose levels are tightly regulated at all times. Gluconeogenesis is the metabolic pathway dedicated to glucose synthesis from non-hexose precursors. Gluconeogenesis is critical for glucose homoeostasis, particularly during fasting or stress conditions. The renal contribution to systemic gluconeogenesis is increasingly recognized. During the post-absorptive phase, the kidney accounts for similar to 40% of endogenous gluconeogenesis, occurring mainly in the kidney proximal tubule. The main substrate for renal gluconeogenesis is lactate and the process is regulated by insulin and cellular glucose levels, but also by acidosis and stress hormones. The kidney thus plays an important role in the maintenance of glucose and lactate homoeostasis during stress conditions. The impact of acute and chronic kidney disease and proximal tubular injury on gluconeogenesis is not well studied. Recent evidence shows that in both experimental and clinical acute kidney injury, impaired renal gluconeogenesis could significantly participate in systemic metabolic disturbance and thus alter the prognosis. This review summarizes the biochemistry of gluconeogenesis, the current knowledge of kidney gluconeogenesis, its modifications in kidney disease and the clinical relevance of this fundamental biological process in human biology.